Compositions and methods for treating and preventing hepatitis b and d

Abstract

Disclosed herein are immunogenic compositions or product combinations of engineered hepatitis B and hepatitis D nucleic acids, genes, peptides, or proteins that can be used to elicit an immune response against a hepatitis B and/or hepatitis D infection. Also disclosed are methods of using the immunogenic compositions or product combinations in subjects to generate immune responses against HBV and/or HDV by administering the compositions or combinations, for example, with a nucleic acid prime and polypeptide boost approach.

1 . A polypeptide comprising at least one hepatitis D antigen (HDAg) polypeptide sequence and at least one PreS1 polypeptide sequence, wherein each of the at least one HDAg polypeptide sequence is a C211S mutant HDAg polypeptide sequence. 
     
     
         2 - 56 . (canceled) 
     
     
         57 . The polypeptide of  claim 1 , wherein the at least one HDAg polypeptide sequence comprises the sequence of HDAg genotype 1 A C211S (SEQ ID NO: 47), HDAg genotype 1 B C211S (SEQ ID NO: 48), HDAg genotype 2 A C211S (SEQ ID NO: 49), HDAg genotype 2 B C211S (SEQ ID NO: 50), or any combination thereof. 
     
     
         58 . The polypeptide of  claim 1 , wherein the at least one PreS1 polypeptide sequence comprises the sequence of SEQ ID NO: 11 or SEQ ID NO: 12, or both. 
     
     
         59 . The polypeptide of  claim 1 , wherein the polypeptide comprises one or more epitope tags. 
     
     
         60 . The polypeptide of  claim 1 , wherein the polypeptide comprises a sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% homology or sequence identity to the sequence of any one of SEQ ID NO: 72-95, 140-141, 145-147, 163-177, or 187-195. 
     
     
         61 . The polypeptide of  claim 1 , wherein the polypeptide is recombinantly expressed. 
     
     
         62 . The polypeptide of  claim 1 , wherein the polypeptide is recombinantly expressed in a mammalian, bacterial, yeast, insect, or cell-free system. 
     
     
         63 . The polypeptide of  claim 62 , wherein the polypeptide is recombinantly expressed in  E. coli.    
     
     
         64 . A nucleic acid operon comprising two or more genes, wherein each of the two or more genes comprise at least one HDAg nucleic acid sequence and at least one PreS1 nucleic acid sequence, and wherein each of the two or more genes comprises a 5′ ribosome binding site, wherein the at least one HDAg nucleic acid sequence encodes a polypeptide comprising a C211 mutation. 
     
     
         65 . The nucleic acid operon of  claim 64 , wherein the at least one HDAg nucleic acid sequence and/or the at least one PreS1 nucleic acid sequence are codon optimized to reduce the number of repeat sequences. 
     
     
         66 . The nucleic acid operon of  claim 64 , wherein the at least one HDAg nucleic acid sequence comprises the sequence of HDAg genotype 1 A C211S (SEQ ID NO: 43), HDAg genotype 1 B C211S (SEQ ID NO: 44), HDAg genotype 2 A C211S (SEQ ID NO: 45), HDAg genotype 2 B C211S (SEQ ID NO: 46), or any combination thereof. 
     
     
         67 . The nucleic acid operon of  claim 64 , wherein the at least one PreS1 nucleic acid sequence comprise the sequence of SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, or any combination thereof. 
     
     
         68 . The nucleic acid operon of  claim 64 , wherein each of the two or more genes further encode one or more epitope tags. 
     
     
         69 . The nucleic acid operon of  claim 64 , wherein the nucleic acid operon comprises a sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% homology or sequence identity to the sequence of any one of SEQ ID NO: 96-101 or 196-199. 
     
     
         70 . The nucleic acid operon of  claim 64 , wherein the two or more genes encode two or more polypeptides comprising the sequence of any one of SEQ ID NO: 102-133 or 200-203. 
     
     
         71 . The nucleic acid operon of  claim 70 , wherein each of the two or more genes do not encode one or more epitope tags. 
     
     
         72 . A product comprising the polypeptide of  claim 1 , and a nucleic acid comprising at least one nucleic acid sequence encoding HDAg and at least one nucleic acid sequence encoding PreS1, wherein each of the at least one HDAg nucleic acid sequence encodes a polypeptide comprising a C211 mutation. 
     
     
         73 . The product of  claim 72 , wherein the at least one HDAg nucleic acid sequence or the at least one PreS1 nucleic acid sequence are codon optimized to minimize or reduce the number of repeat sequences. 
     
     
         74 . The product of  claim 72 , wherein the nucleic acid further encodes one or more epitope tags. 
     
     
         75 . The product of  claim 72 , wherein the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% homology or sequence identity to the sequence of any one of SEQ ID NO: 60-71, 138-139, 142-144, 148-162, or 178-186. 
     
     
         76 . The product of  claim 72 , wherein the nucleic acid is DNA. 
     
     
         77 . The product of  claim 72 , wherein the nucleic acid is RNA. 
     
     
         78 . The polypeptide of  claim 1 , wherein at least one of the HDAg polypeptide sequences in the polypeptide comprises a C211S mutation.